We plan to investigate the cause and prevention or cardiac arrhythmias, placing special emphasis on the role of the loss of resting potential in setting the stage for slow response action potentials that depend on the slow inward current. We will use electrophysiological techniques for these studies, such as intracellular recording, stimulation and the recording of action potentials. We will study the phenomenon of continous fall in resting potential, in which cells of the heart show a virtually continuous fall in resting potential from -90mV to -50mV or a virtually discontinous increase from -50mV to -90mV. These shifts result from a steeply voltage-dependent change in potassium conductance. We plan to test antiarrhythmic drugs to ascertain whether such drugs have an effect on the after-depolarization. We will also study antrioventricular nodal reentrant tachycardia to ascertain whether antiarrhythmic node. Further studies include an examination of the mechanism of action of the optical isomers of verapamil to ascertain whether they differ from the racemic mixture in their effects on normal and slow response action potentials and arrhythmias. We will also investigate the role played by electrogenic sodium extrusion in the maintenance of membrane potential.